This work will continue investigaitons of platelet leukocyte interactions as a mediator of host defense with specific reference to platelet serotonin. An animal model of the Chediak-Higashi (CH) syndrome is used. Here, a platelet defect, absence of serotonin and a neutrophil defect, impaired chemotaxis and microbial killing are present. Preliminary work demonstrated that both normal mouse platelets and serotonin corrected the CH neutrophil defect. This correlation of function occurred in vivo and in vitro and appears to be specifically associated with the presence of serotonin. The specificity of serotonin will be further explored through the use of agents which inhibit its synthesis, release and/or catabolism. The use of agents which inhibit synthesis or release would be expected to be associated with platelets which are unable to correct CH leukocyte function. Agents which impair catabolism would be expected to prolong the usefulness of serotonin infusions. Other proposed studies are to document the mechanisms of action of serotonin by evaluation of leukocyte microtubule function. Microtubule function is known to be impaired in CH leukocytes and serotonin is known to affect intracellular cyclic nucleotide concentrations, which in turn affect microtubules. We expect that serotonin and thus platelets, mediate their effect through this mechanism.